Quorum-sensing inhibitors as anti-pathogenic drugs

TY - JOUR

T1 - Quorum-sensing inhibitors as anti-pathogenic drugs

AU - Rasmussen, Thomas B

AU - Givskov, Michael

N1 - Keywords: 4-Butyrolactone; Animals; Anti-Bacterial Agents; Bacterial Proteins; Biofilms; Cell Communication; Ligases; Metalloendopeptidases; Neutrophils; Pseudomonas aeruginosa; Repressor Proteins; Trans-Activators; Virulence

PY - 2006

Y1 - 2006

N2 - Quorum-sensing (QS) signalling systems of pathogens are central regulators for the expression of virulence factors and represent highly attractive targets for the development of novel therapeutics. In Pseudomonas aeruginosa, QS systems are also involved in elevated antibiotic tolerance of biofilms as well as elevated tolerance to the activity of the innate immune system. Gram-negative bacteria commonly use N-acyl homoserine lactones (AHL) as QS signal molecules. The use of signal molecule based drugs to attenuate bacterial pathogenecity rather than bacterial growth is attractive for several reasons, particularly considering the emergence of increasingly antibiotic-resistant bacteria. Compounds capable of this type of interference have been termed anti-pathogenic drugs. A large variety of synthetic AHL analogues and natural products libraries have been screened and a number of QS inhibitors (QSI) have been identified. Promising QSI compounds have been shown to make biofilms more susceptible to antimicrobial treatments, and are capable of reducing mortality and virulence as well as promoting clearance of bacteria in experimental animal models of infection.

AB - Quorum-sensing (QS) signalling systems of pathogens are central regulators for the expression of virulence factors and represent highly attractive targets for the development of novel therapeutics. In Pseudomonas aeruginosa, QS systems are also involved in elevated antibiotic tolerance of biofilms as well as elevated tolerance to the activity of the innate immune system. Gram-negative bacteria commonly use N-acyl homoserine lactones (AHL) as QS signal molecules. The use of signal molecule based drugs to attenuate bacterial pathogenecity rather than bacterial growth is attractive for several reasons, particularly considering the emergence of increasingly antibiotic-resistant bacteria. Compounds capable of this type of interference have been termed anti-pathogenic drugs. A large variety of synthetic AHL analogues and natural products libraries have been screened and a number of QS inhibitors (QSI) have been identified. Promising QSI compounds have been shown to make biofilms more susceptible to antimicrobial treatments, and are capable of reducing mortality and virulence as well as promoting clearance of bacteria in experimental animal models of infection.

U2 - 10.1016/j.ijmm.2006.02.005

DO - 10.1016/j.ijmm.2006.02.005

M3 - Journal article

C2 - 16503194

SN - 1438-4221

VL - 296

SP - 149

EP - 161

JO - International Journal of Medical Microbiology

JF - International Journal of Medical Microbiology

IS - 2-3

ER -